Continuous Opioid Monitoring along with Nerve Agents on a Wearable Microneedle Sensor Array

Abstract

There are urgent needs for sensing devices capable of distinguishing between episodes of opioid overdose and nerve agent poisoning. This work presents a wearable microneedle sensor array for minimally invasive continuous electrochemical detection of opioid (OPi) and organophosphate (OP) nerve agents on a single patch platform. The new multimodal microneedle sensor array relies on unmodified and organophosphorus hydrolase (OPH) enzyme-modified carbon paste (CP) microneedle electrodes for square wave voltammetric (SWV) detection of the fentanyl and nerve agent targets, respectively. Such real-time simultaneous sensing provides distinct unique information, along with attractive analytical performance, including high sensitivity, selectivity, and stability, for real-time on-body OPi–OP analysis. The patch represents the first sensing device capable of continuously monitoring fentanyl down to the nanomolar level through a nanomaterial-based multilayered surface architecture. Applicability of the sensor array toward opioids screening is demonstrated for morphine and norfentanyl. Successful OPi–OP detection conducted in a skin-mimicking phantom gel demonstrates the suitability of the device for rapid on-body sensing. Such progress toward continuous minimally invasive transdermal analysis of drugs of abuse and nerve agents holds promise for rapid countermeasures for protecting soldiers, civilians, and healthcare personnel.

Wearable electrochemical biosensors in North America

“…Efforts aimed at expanding the scope of detectable analytes beyond common metabolites and electrolytes, have led to the detection of stress J o u r n a l P r e -p r o o f hormone cortisol in sweat relying on various recognition elements of bioaffinity-based (Torrente-Rodríguez et al, 2020a) and molecularly imprinted polymer (MIP)-based (Parlak et al, 2018) sensors. Additionally, several studies have reported the detection of various drugs, either therapeutic or illicit, in sweat and ISF samples (Goud et al, 2019;Mishra et al, 2020a;Tai et al, 2019Tai et al, , 2018. Add to these, the studies on utilizing the great potential of electrochemical aptamer-based sensors toward in-vivo detection of drug targets in blood samples of anesthetized animals (Arroyo-Currás et al, 2018;Dauphin-Ducharme et al, 2019).…”

“…4bii). Voltammetric techniques have also been demonstrated for the sensitive detection of opioids and nerve agents (Mishra et al, 2020a), and explosives (Sempionatto et al, 2017a).…”

Microneedle-based devices for point-of-care infectious disease diagnostics

“…There are two design strategies for fabricating in-situ microneedle sensors. The first involves the development of electroactive solid microneedles, while the second uses hollow microneedles to house conventional electrochemical sensing elements, such as modified carbon pastes and fibres 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 . The fabrication of solid microneedle sensors typically employs sputtering or e-beam evaporation to metallise polymeric or metallic microneedles to produce an electroactive surface, which is then functionalised with an appropriate enzyme or coating to selectively detect an analyte 62 .…”

“…Both solid and hollow microneedle-based in-situ sensors have detected therapeutic drugs, electrolytes, alcohol, pH changes, small molecules, including glucose, nitric oxide, ascorbic acid, uric acid, dopamine, glutamate, neurotransmitters and organophosphorus nerve agents 61 , 62 , 66 , 93 , 122 , 124 , 125 , 126 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 . For solid microneedle biosensors, recognition elements such as enzymes are typically cross-linked to the microneedle surface using covalent cross-liking chemistries to protect them from accidental removal or degradation during skin application 142 .…”

Nanomaterials and Cross-Cutting Technologies for Fostering Smart Electrochemical Biosensors in the Detection of Chemical Warfare Agents

“…The author declares no conflict of interest. The novel approach using a wearable microneedle sensor array to distinguish between opioid overdose and nerve agent poisoning was reported in the Journal of American Chemical Society in 2020 by the same group [39]. The microneedle array was fabricated by using a hollow microneedle working electrodes allowing (i) for direct voltammetric detection of fentanyl-based on oxidative dealkylation of the piperidine tertiary amine and norfentanyl production with a peak at +0.7 V, and (ii) for square wave voltammetry of the organophosphate hydrolase-by product, i.e., p-nitrophenol using methyl paraoxon as a nerve agent simulant, with a peak at ca.…”